Abstract
AMPA-type glutamate receptors (AMPA-Rs) mediate a majority of excitatory synaptic transmission in the brain. In hippocampus, most AMPA-Rs are hetero-oligomers composed of GluR1/GluR2 or GluR2/GluR3 subunits. Here we show that these AMPA-R forms display different synaptic delivery mechanisms. GluR1/GluR2 receptors are added to synapses during plasticity; this requires interactions between GluR1 and group I PDZ domain proteins. In contrast, GluR2/GluR3 receptors replace existing synaptic receptors continuously; this occurs only at synapses that already have AMPA-Rs and requires interactions by GluR2 with NSF and group II PDZ domain proteins. The combination of regulated addition and continuous replacement of synaptic receptors can stabilize long-term changes in synaptic efficacy and may serve as a general model for how surface receptor number is established and maintained.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Blotting, Western
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Carrier Proteins / metabolism
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Cell Line
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Excitatory Amino Acid Agonists / pharmacology
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Humans
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In Vitro Techniques
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Kainic Acid / pharmacology
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Long-Term Potentiation / physiology
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Models, Biological
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Molecular Sequence Data
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N-Ethylmaleimide-Sensitive Proteins
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Neuronal Plasticity / physiology
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Patch-Clamp Techniques
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Protein Structure, Tertiary
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Protein Subunits*
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Protein Transport / physiology*
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Pyramidal Cells / cytology
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Pyramidal Cells / drug effects
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Pyramidal Cells / metabolism*
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Rats
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Receptors, AMPA / chemistry
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Receptors, AMPA / genetics
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Receptors, AMPA / metabolism*
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Recombinant Fusion Proteins / metabolism
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Synapses / physiology*
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Transfection
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Vesicular Transport Proteins*
Substances
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Carrier Proteins
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Excitatory Amino Acid Agonists
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Protein Subunits
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Receptors, AMPA
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Recombinant Fusion Proteins
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Vesicular Transport Proteins
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glutamate receptor ionotropic, AMPA 3
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N-Ethylmaleimide-Sensitive Proteins
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Nsf protein, rat
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glutamate receptor ionotropic, AMPA 2
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Kainic Acid
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glutamate receptor ionotropic, AMPA 1